PRAGUE—End-stage renal disease patients on post-dilution online hemodiafiltration (HDF) or high-flux hemodialysis (HD) have the same overall survival and non-fatal cardiovascular (CV) event rates, new findings show.
HDF patients with substitution volume greater than 17.4 L, however, have better CV and overall survival, Fatih Kircelli, MD of the Division of Nephrology at Ege University School of Medicine in Izmir, Turkey reported at the 48th Congress of the European Renal Association-European Dialysis and Transplant Association during a late-breaking clinical trials session.
Patients on HD have unacceptably high morbidity and mortality. Supposed advantages of HDF including better clearance of middle, larger-sized, and protein-bound uremic solutes, better β2-microglobulin removal, better biocompatibility, and reduced inflammatory markers. The researchers compared these two renal replacement modalities in the Turkish HDF Study to look for survival differences. The primary outcomes were a combination of all-cause mortality and new non-fatal CV events.
Patients 18 years or older from 10 HD centers were screened and then randomized to HDF (391 patients) or HD (391 patients) treatment with a planned follow-up of 24 months. To be eligible, patients had to be on maintenance bicarbonate HD three times per week for 12 hours weekly with an achieved mean single pool Kt/V of 1.2 or greater. They could not have a temporary catheter or insufficient vascular access (less than 250 mL/min).
During the study, HDF or HD was performed for four hours thrice weekly with a blood flow rate of 250 to 400 mL/min and a target substitution volume of greater than 15 L per session. The two treatment groups were well matched for age (56 years), gender, diabetes (33%-36%), vascular access (95% arteriovenous fistula), CV history (25.7%-27.2%), dialysis duration (about 58 months), body mass index, adequate control of blood pressure and anemia, and interdialytic weight gain.
During follow-up, the researchers found a blood flow rate of 318 mL/min in the HDF group and 303 mL/min in the HD group. Both groups had a mean substitution volume of 17.2 L per session, with a range of 9.8 L to 20.3 L (93% achieving greater than 15 L per session). Ninety-nine patients in the HDF group transferred either to HD or to another center, and 84 patients in the HD group transferred to another center.
Better outcomes with higher efficiency HDF
In the HDF and HD arms, 61 and 73 patients, respectively, achieved the primary endpoint. Event-free survival was about 80% at 40 months. Overall mortality was 6.98 and 8.80 per 100 patient-years in the HDF and HD arms, respectively. CV mortality was 4.30 and 5.96 per 100 patient-years, with no differences in hospitalization rates or intradialytic hypotension. None of these between-group differences was statistically significant.
The required dose of erythropoiesis stimulating agent was significantly lower for the HDF patients (2,282 U/week) than for the HD patients (2,852 U/week).
When patients were stratified in subgroup analyses by the presence of diabetes, a history of cardiovascular disease, or serum albumin levels less than 4 g/dL, the researchers found no differences in the primary outcome or overall or cardiovascular survival. When patients were stratified according to whether their median substitution volume was above 17.4 L per session (high efficiency group) or 17.4 L or less (low efficiency group), the researchers observed no significant difference in the primary outcome.
However, high efficiency online HDF was associated with significantly better overall and cardiovascular survival, he said. The high efficiency group had a 46% lower risk of overall mortality and a 71% lower risk for CV mortality. In the low efficiency group, more patients had diabetes, lower serum albumin levels, and higher hemoglobin levels.
In light of post-dilutional online HDF providing better overall survival and CV survival when performed in high-efficiency mode, Dr. Kircelli concluded that reaching higher convection volumes appears “to be an essential issue in post-dilution online HDF” treatment.
In response to a question from the audience, Dr. Kircelli explained that patients were not randomized to high or low efficiency HDF but that the stratification according to their achieved fluid substitution volumes was done in a post hoc fashion.
Markus Ketteler, MD, Chief of the Division of Nephrology at Klinikum Coburg in Coburg, Germany, explained to Renal & Urology News that if the stratification was made based on the capacity of the shunts or the fistulas to transport larger volumes, “then it is very likely or quite likely that patients were selected who had a better circulation.” This could account for the better outcomes seen in the high efficiency HDF group. He also said the focus should be on the primary outcome and not on endpoints that were not originally specified for the trial.